The long term goal of our research is to understand how animals sense and react to environmental cues. The current proposal focuses on the sense of light, a sensory modality critical for animal life. Light is detected by photoreceptor cells in he retina where they mediate image-forming vision. In addition, photoreceptor cells, particularly those extra-ocular photoreceptor cells, mediate non-image-forming functions such as phototaxis, circadian rhythms, pupil constriction, and magnetic orientation. While the image-forming vision has been extensively characterized, relatively little is known about the mechanisms of the non-image-forming functions of photoreceptor cells. The nematode C. elegans is a popular genetic model organism for the study of sensory transduction such as chemosensation (e.g. olfaction and taste) and mechanosensation (e.g. touch sensation and proprioception). However, C. elegans were believed to lack the sense of light, as they live in darkness (soil) and also do not have eyes. Interestingly, we have recently demonstrated that these eyeless animals, surprisingly, possess the sense of light and engage in photosensory behavior (phototaxis) that allows them to avoid lethal doses of light and also provides a potential mechanism for retaining them in dark environments. Intriguingly, a similar phenomenon also exists in other organisms, such as Drosophila larva, which requires extra-ocular photoreceptor cells. Here we propose to elucidate the mechanisms underlying photosensation in C. elegans. We will identify all the photoreceptor cells required for phototaxis, determine the signaling mechanisms in photoreceptor cells, and identify the photoreceptor protein. We will take a multidisciplinary approach combining genetics, behavioral analysis, pharmacology, biochemistry, and electrophysiology. The proposed study will provide novel insights into the mechanisms of the non-image-forming functions of photoreceptor cells in mammals. PUBLIC HEALTH RELEVANCE: Abnormalities in photosensation lead to a variety of human diseases, including eye diseases and sleep disorders. The proposed studies will facilitate our understanding of photosensation and related diseases.